Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
J Med Chem. 2011 Dec 22;54(24):8299-304. doi: 10.1021/jm200691d. Epub 2011 Nov 23.
Eight monomeric congeners, related to the multitarget lead candidate memoquin, were prepared and evaluated at multiple targets to determine their profile against Alzheimer's disease. 2-4 bind to AChE with similar low nanomolar affinities and function as effective inhibitors of amyloid aggregation. The most potent monovalent ligand 2 also inhibits BACE-1 in vitro and APP metabolism in primary chicken telencephalic neurons.
制备了 8 个与多靶点先导候选物 memoquin 相关的单体同系物，并在多个靶点进行了评估，以确定它们在治疗阿尔茨海默病方面的作用。2-4 与 AChE 结合具有相似的低纳摩尔亲和力，并作为有效的淀粉样蛋白聚集抑制剂。最有效的单价配体 2 还在体外抑制 BACE-1 和原代鸡大脑神经元中 APP 的代谢。
